Effective therapeutic methods for the treatment of cellular disorders such as cancer have been the object of intensive research. Conventional therapy employs surgery, radiation and chemotherapy. Each of these methods suffers a serious drawback in that it is not highly selective between healthy and cancerous cells. In order to be effective, these methods kill or remove large amounts of healthy tissue. Furthermore, chemotherapy adversely affects the immune system so that death or serious illness often arises from fungal, bacterial or viral infections.
The development of monoclonal antibodies has opened the possibility of selectively delivering therapeutic agents or diagnostic agents to specific target cells. Monoclonal antibodies are immunoglobulins of well-defined chemical structure. A characteristic feature of monoclonal antibodies is reproducability of function and high specificity.
Radioiodine bound directly to monoclonal antibodies has been used for diagnosis and therapy. Iodine-131 has had some therapeutic success for large tumors, but radioiodine labled antibodies have been ineffective in the treatment of small tumor foci or metastases. In addition, specifically bonded antibodies are relatively rapidly catabolized by the target cell. Catabolism, therefore, leads to the incorporation of metabolized iodine in the excretory organs, i.e., kidney, bladder and stomach. In addition, attempts to transport toxins via monoclonal antibodies to tumor cells have not resulted in a successful therapeutic method.
It has been suggested in the literature that diethylenetriaminepentaacetic acid (DTPA) can form stable metal complexes when attached to protein. Krejcarek et al., 77 Biochem. & Biophys. Res. Commun. 581 (1977). Imaging of target sites in vivo with radiometal-DTPA conjugated polyclonal antibodies prepared according to the method of Krejcarek have been reported by Khaw et al., 209 Science 295 (1980). Despite separation, by gel chromatography and dialysis, of free and chelated metal from metal chelate conjugated polyclonal antibodies the gamma images included in the article show that a high proportion of the radiometal localized in the liver.
Diagnostic methods are adversely affected unless substantially all of the compound used for labeling is attracted to the desired target. Any of the labeling compound that does not attach to the target can create an undesirable background. If radiometals are used, they can disseminate in the body and have the potential of doing damage.